Sensitization of adenylate cyclase by short-term activation of 5-HT1A receptors.
Sensitization of adenylate cyclase by short-term activation of 5-HT1A receptors.
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DOI：
10.1016/s0898-6568(03)00115-3
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发表时间：
2003-12
影响因子：
4.8
通讯作者：
Joshua G. Lisinicchia;V. Watts
中科院分区：
文献类型：
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作者：
Joshua G. Lisinicchia;V. Watts
长期（18小时）激活5-HT 1A受体改变5-HT 1A受体-G蛋白偶联，并导致腺苷酸环化酶的异源致敏。相反，短期（2小时）5-HT 1A受体激活对随后的腺苷酸环化酶活性的影响尚未确定。本研究检查并表征了CHO-5-HT 1A细胞短期激活后5-HT 1A受体诱导的异源致敏作用。短期激活5-HT 1A受体与完全激动剂，以及部分激动剂，丁螺环酮，显着增强随后毛喉素刺激的环AMP积累。用5 HT处理30分钟后，这种异源致敏作用明显，并且在激动剂处理2小时后似乎接近最大。致敏的特征是剂量依赖性增加毛喉素刺激的环磷酸腺苷的积累，并防止通过WAY 100635或百日咳毒素治疗。5-HT 1A激动剂诱导异源致敏的能力没有被先前显示的调节5-HT 1A介导的环AMP积累抑制的试剂显著改变。
Long-term (18 h) activation of 5-HT1A receptors alters 5-HT1A receptor-G protein coupling and leads to heterologous sensitization of adenylate cyclase. In contrast, the effects of short-term (2 h) 5-HT1A receptor activation on subsequent adenylate cyclase activity have not been determined. The present study examined and characterized 5-HT1A receptor-induced heterologous sensitization following short-term activation in CHO-5-HT1A cells. Short-term activation of 5-HT1A receptors with full agonists, as well as the partial agonist, buspirone, markedly enhanced subsequent forskolin-stimulated cyclic AMP accumulation. This heterologous sensitization was evident after 30 min treatment with 5HT and appeared to be near maximal following 2 h agonist treatment. Sensitization was characterized by a dose-dependent increase in forskolin-stimulated cyclic AMP accumulation and was prevented by WAY 100635 or by pertussis toxin treatment. The ability of the 5-HT1A agonists to induce heterologous sensitization was not significantly altered by agents shown previously to modulate 5-HT1A-mediated inhibition of cyclic AMP accumulation.